简介：TcellhomeostasiscommonlyreferstothemaintenanceofrelativelystableTcellnumbersintheperipherallymphoidorgans.AmongthelargenumbersofTcellsintheperiphery,Tcellsexhibitstructuraldiversity,I.e.,theexpressionofadiverserepertoireofTcellreceptors(TCRs),andfunctionaldiversity,I.e.,thepresenceofTcellsatna(I)ve,effector,andmemorydevelopmentalstages.AlthoughthehomeostasisofTcellnumbershasbeenextensivelystudied,investigationofthemechanismsunderlyingthemaintenanceofstructuralandfunctionaldiversityofTcellsisstillatanearlystage.ThefundamentalfeaturethroughoutTcelldevelopmentistheinteractionbetweentheTCRandeitherselforforeignpeptidesinassociationwithMHCmolecules.Inthisreview,wepresentevidenceshowingthathomeostasisofTcellnumberanddiversityismediatedthroughcompetitionforlimitingresources.ThenumberofTcellsismaintainedthroughcompetitionforlimitingcytokines,whereasthediversityofTcellsismaintainedbycompetitionforself-peptide-MHCcomplexes.Inotherwords,diversityoftheself-peptiderepertoirelimitsthestructural(TCR)diversityofaTcellpopulation.Wespeculatethatcognatelowaffinityself-peptides,actingasweakagonistsandantagonists,regulatethehomeostasisofTcelldiversitywhereasnon-cognateornullpeptideswhichareextremelyabundantforanygivenTCR,maycontributetothehomeostasisofTcellnumberbyprovidingsurvivalsignals.Moreover,self-peptidesandcytokinesmayformspecializednichesfortheregulationofTcellhomeostasis.

简介：狗作为他们与人的关系的后果在强壮的人工的选择下面。品种之间的差别是明显的那能在精液的特征被反映。现在的学习是在在狗的七个明确的品种之间的精子头morphometry评估差别：英国牛犬，Chihuahua，德国牧人，北美东北部的半岛Retriever，西班牙的一种猛犬，Staffordshire猎犬，和Valencian老鼠狩猎狗。精液样品被与Diff-Quik染色的手淫和油迹获得。Morphometric分析(CASA-Morph)生产了四种尺寸和四个形状参数。长度，椭圆状，和延伸显示出品种之间的更高的差别。MANOVA在所有品种之中揭示了差别。就整个数据集而言，主要部件分析(PCA)证明PC1与头形状和PC2有关缩放。Procluster分析显示了英国牛犬是最孤立的品种，由德国牧人列在后面。由品种的PCA品种显示出有与而英国牛犬，巴伦西亚老鼠狩猎狗，和德国牧人有与尺寸有关的PC1，缩放的形状和PC2和塑造的PC2有关的PC1的Chihuahua，北美东北部的半岛Retriever，西班牙的一种猛犬，和Staffordshire猎犬。为在他们之间的簇组织和距离的dendrogram显示了英国牛犬与品种的其余部分被分开。狗精液上的未来工作必须在品种精子特征考虑大差别。结果在狗的种系发生、进化的研究上为未来工作提供一个底，基于他们的精液的特征。

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简介：AbstractCoronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), declared as a pandemic due to its rapid spread worldwide. In this study, we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2, using 22 virus genome sequences reported by three different laboratories in Morocco till June 7,2020, as well as 40,366 virus genomes from all around the world. The SARS-CoV-2 genomes from Moroccan patients revealed 62 mutations, of which 30 were mis-sense mutations. The mutations Spike_D614G and NSP12_P323L were present in all the 22 analyzed sequences, followed by N_G204R and N_R203K, which occurred in 9 among the 22 sequences. The mutations NSP10_R134S, NSP15_D335N, NSP16_I169L, NSP3_L431H, NSP3_P1292L and Spike_V6F occurred once in Moroccan sequences, with no record in other sequences worldwide. Phylogenetic analyses revealed that Moroccan SARS-CoV-2 genomes included 9 viruses belonging to Clade 20A, 9 to Clade 20B and 2 to Clade 20C, suggesting that the epidemic spread in Morocco did not display a predominant SARS-CoV-2 route. Therefore, multiple and unrelated introductions of SARS-CoV-2 into Morocco through different routes have occurred, giving rise to the diversity of virus genomes in the country. Further, in all probability, the SARS-CoV-2 circulated in a cryptic way in Morocco, starting from January 15, 2020 before the first case was officially discovered on March 2, 2020.

简介：AbstractBackground:Giardia intestinalis is one of the most common causes of diarrhoea worldwide. Molecular techniques have greatly improved our understanding of the taxonomy and epidemiology of this parasite. Co-infection with mixed (sub-) assemblages has been reported, however, Sanger sequencing is sometimes unable to identify shared subtypes between samples involved in the same epidemiologically linked event, due to samples showing multiple dominant subtypes within the same outbreak. Here, we aimed to use a metabarcoding approach to uncover the genetic diversity within samples from sporadic and outbreak cases of giardiasis to characterise the subtype diversity, and determine if there are common sequences shared by epidemiologically linked cases that are missed by Sanger sequencing.Methods:We built a database with 1109 unique glutamate dehydrogenase (gdh) locus sequences covering most of the assemblages of G. intestinalis and used gdh metabarcoding to analyse 16 samples from sporadic and outbreak cases of giardiasis that occurred in New Zealand between 2010 and 2018.Results:There is considerable diversity of subtypes of G. intestinalis present in each sample. The utilisation of meta-barcoding enabled the identification of shared subtypes between samples from the same outbreak. Multiple variants were identified in 13 of 16 samples, with Assemblage B variants most common, and Assemblages E and A present in mixed infections.Conclusions:This study showed that G. intestinalis infections in humans are frequently mixed, with multiple subtypes present in each host. Shared sequences among epidemiologically linked cases not identified through Sanger sequencing were detected. Considering the variation in symptoms observed in cases of giardiasis, and the potential link between symptoms and (sub-) assemblages, the frequency of mixed infections could have implications for our understanding of host-pathogen interactions.

简介：AbstractThe recently emerged Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has quickly spread around the world. Although many consensus mutations of the Omicron variant have been recognized, little is known about its genetic variation during its transmission in the population. Here, we comprehensively analyzed the genetic differentiation and diversity of the Omicron variant during its early outbreak. We found that Omicron achieved more structural variations, especially deletions, on the SARS-CoV-2 genome than the other four variants of concern (Alpha, Beta, Gamma, and Delta) in the same timescale. In addition, the Omicron variant acquired, except for 50 consensus mutations, seven great new non-synonymous nucleotide substitutions during its spread. Three of them are on the S protein, including S_A701V, S_L1081V, and S_R346K, which belong to the receptor-binding domain (RBD). The Omicron BA.1 branch could be divided into five divergent groups spreading across different countries and regions based on these seven novel mutations. Furthermore, we found that the Omicron variant possesses more mutations related to a faster transmission rate than the other SARS-CoV-2 variants by assessing the relationship between the genetic diversity and transmission rate. The findings indicated that more attention should be paid to the significant genetic differentiation and diversity of the Omicron variant for better disease prevention and control.

简介：AbstractSFTS virus (SFTSV) is a novel bunyavirus, which was discovered as the etiological agent of severe fever with thrombocytopenia syndrome (SFTS) in China in 2009, and was now prevalent in at least 25 provinces in China. SFTS was subsequently identified in South Korea and Japan in 2012. To explore the molecular evolution and genetic characteristics of this newly identified pathogen, we reported 72 whole genome sequences of SFTSV, and built a dataset of SFTSV genome sequences containing 292 L-segment, 302 M-segment and 502 S-segment. We clearly divided SFTSV into six genotypes, Genotype A-F. It was found that genotype F was the dominant epidemic genotype of Japan, South Korea, and Zhejiang province of China. The coalescent analysis supported that SFTSV originated in the early 18th century from Zhejiang province, and Genotype F was the most primitive one. Henan, Hubei, and Anhui provinces which are located in Dabie Mountain area were mainly epidemic of Genotype A, which emerged relatively late but distributed widely. A total of 37 recombination events were identified, making SFTSV with a high recombination frequency (L segment 5.1%, M segment 3.6%, S segment 0.8%) among negative-strand segmented RNA viruses. It was identified that 19 reassortant strains belonged to 12 reassortment forms of SFTSV genome containing 6 newly identified forms. The reassortment virus and recombination in tick were both found for the first time. We also found many of genotype-specific mutation sites, 7 of which could be considered as potential molecular marker for genotype classification. This study promoted a more comprehensive understanding of the phylogeny and origin, and the genetic diversity of SFTSV, and it could help the studies of other newly discovered tick-borne bunyavirus as reference data and research ideas.

简介：AbstractBackground:Recent cardiovascular outcome trials (CVOTs) changed the therapeutic strategy of guidelines for type 2 diabetes. We compared the characteristics of patients from real-world hospital settings with those of participants in recent pragmatic randomized trials.Methods:This electronic medical record (EMR)-based retrospective observational study investigated the data of patients with diabetes from inpatient and outpatient settings in West China Hospital of Sichuan University from January 1, 2011, to June 30, 2019. We identified patients meeting the inclusion criteria of a pragmatic randomized trial (EMPA-REG OUTCOME) based on EMRs and compared their baseline characteristics with those of the trial participants. The cutoff for the clinical significance of each characteristic was set as its minimal clinically important difference based on expert consultation.Results:We included 48,257 inpatients and 36,857 outpatients with diabetes and found that 8389 (17.4%) inpatients and 2646 (7.2%) outpatients met the inclusion criteria for the EMPA-REG OUTCOME trial. Compared with the trial population, the realworld inpatients meeting the eligibility criteria of the EMPA-REG OUTCOME had similar age, blood pressure, and lipid profiles but comprised of fewer males, metformin users, anti-hypertensive drug users, and aspirin users, and had a lower body mass index. The group of outpatients meeting the eligibility criteria had fewer males, similar age, fewer metformin users, fewer insulin users, fewer anti-hypertensive drug users, and fewer aspirin users compared with the trial population.Conclusions:The trial population in EMPA-REG OUTCOME represents only a small portion of patients with diabetes from the inpatient and outpatient departments of a Chinese tertiary medical center. Evidence localization in different clinical settings and validation are essential to enabling extrapolation of the results from CVOTs in patients with diabetes to Chinese clinical practice.

简介：决定区域3的补充(CDR3)的分析一些由immunoscopespectratyping技术的T淋巴细胞受体(TCR)成功地被使用了在自体免疫的疾病和感染疾病调查TCR的差异。在这研究，我们由immunoscopespectratyping技术在四个正常志愿者的人的外部血淋巴细胞为所有32个TCRAV基因家庭调查了CDR3长度分发的模式。PCR产品在1.5%agarose胶化电气泳动上展出了一个卑微的乐队，这被发现。每个TCRAV家庭在6%上展出了超过8个乐队定序胶化电气泳动。所有TCRAV家庭的CDR3spectratyping与不同CDR3长度显示出标准Gaussian分布，并且CDR3的表示频率在基因家庭之中是类似的。大多数在TCRAV家庭的CDR3在框架重新结合。然而，一些CDR3显示出外面框架基因重新整理。另外，我们发现在一些TCRAV家庭，在最长的CDR3和最短的CDR3之间有18氨基酸差异。这些结果可能是有用的进一步在健康人和疾病状态学习人的TCR基因，TCRCDR3基因全部剧目，和全部剧目飘移的再结合机制。

简介：AbstractBackground:Re-biopsy of metastasis in advanced breast cancer (ABC) has become an international convention to assist the diagnosis and evaluation of tumor heterogeneity. This study aimed to detect diagnostic diversity and inconsistencies among estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression levels between primary and metastatic lesions.Methods:We conducted a retrospective analysis of 1670 cases of ABC patients who had undergone at least one lesion re-biopsy from January 2010 to December 2018. The pathological diagnosis of biopsies, distribution of biopsy sites, and severe puncture complications at each site were collected. In addition, the inconsistency rates and related factors of ER, PR, and HER2 expression between primary and metastatic lesions were analyzed fully considering patients’ demographic profiles and disease characteristics.Results:In total, 1670 cases of breast cancer (BC) patients diagnosed by pathology underwent one to four biopsies of recurrences or metastases in different sites or at different stages during the rescue treatment, producing 2019 histopathological specimens which were analyzed in the study. Pathological diagnosis showed that eight patients had benign pathological diagnoses, 11 patients had second primary malignant tumors but without recurrences of breast cancer, and 17 patients had pathologically confirmed breast cancer recurrences combined with second primary cancer. In 1173 patients who presented ER, PR, and HER2 expressions in primary and metastatic lesions, the inconsistency rates of ER, PR, and HER2 were 17.5% (205/1173), 31.3% (367/1173), and 13.9% (163/1173), respectively. The multivariate analysis showed that the age at the onset of breast cancer or adjuvant endocrine therapy was an independent factor affecting changes in PR expression level. Except one liver puncture with local hemorrhage and two lung punctures with hemopneumothorax, no other severe puncture complications occurred in 1950 non-surgical rebiopsies.Conclusions:The pathological diagnosis of metastasis re-biopsy of ABC was diverse, and the ER, PR, and HER2 expression levels were inconsistent between primary and metastatic lesions. Therefore, more attention should be paid to perform biopsies of relapsed and metastatic breast cancers routinely in clinical practice.

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